Neurocrine Biosciences, Inc. has initiated a phase II clinical trial for NBI-98854 (valbenazine), a highly selective small molecule Vesicular Monoamine Transporter 2 (VMAT2) inhibitor, in children and adolescents with Tourette syndrome.
The T-Force GREEN study is a randomized, double-blind, placebo-controlled, multi-dose, parallel group, study of up to 90 children and adolescents. Subjects will receive once-daily dosing of valbenazine during a six-week treatment period to assess the safety, tolerability and efficacy of valbenazine in pediatric Tourette patients. The primary endpoint of this study is the change from baseline of the Yale Global Tic Severity Scale between placebo and active treatment groups at the end of week six. Data readout from this study is expected later in 2016.
"Following the favorable results from our two-week T-Force study of valbenazine in pediatric Tourette patients, we are launching the T-Force GREEN study assessing children and adolescents over six weeks of continuous dosing," said Christopher F. O'Brien, Chief Medical Officer of Neurocrine Biosciences. "This study, coupled with the ongoing T-Forward study of adults with Tourette syndrome, will elucidate trial design, efficacy and safety outcomes for discussion with regulatory authorities on the utilization of valbenazine in Tourette syndrome. Additionally, the ongoing Kinect studies of valbenazine in patients with tardive dyskinesia will support our anticipated NDA filing of valbenazine for tardive dyskinesia later this year."
The T-Force GREEN study is a multicenter, randomized, double-blind, placebo-controlled, multi-dose, parallel group, Phase II study to evaluate the safety, tolerability and efficacy of NBI-98854 in up to 90 pediatric patients with moderate to severe Tourette syndrome. Two once-daily fixed doses of NBI-98854 will be evaluated vs. placebo in a 1:1:1 randomization. The three-arm study will evaluate up to 45 children and 45 adolescents over six weeks of dosing followed by two weeks off-drug at approximately 40 study centers in the United States. The primary endpoint of this study is the change from baseline of the Yale Global Tic Severity Scale between placebo and active treatment groups at the end of week six. Tourette symptoms will also be evaluated via the Rush Video-Based Tic Rating Scale, Premonitory Urge for Tics Scale as well as Clinical Global Impression scales, among others.
Tourette syndrome is a neurological disorder that consists of rapid, non-rhythmic stereotyped motor and vocal tics. Motor tics are typically characterized by facial grimacing, head jerks, extremity movements and other dystonic movements. Vocal tics typically include grunting, throat clearing, and repeating words and phrases. The average age at onset for Tourette syndrome is at six years, with symptoms reaching their peak severity at approximately age ten. Tourette syndrome is more commonly diagnosed in males than females and may be associated with attention deficit hyperactivity disorder and obsessive compulsive disorder. There are approximately 400,000 people with Tourette syndrome in the United States.
VMAT2 is a protein concentrated in the human brain that is primarily responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre-synaptic neurons. Valbenazine (NBI-98854), developed in the Neurocrine laboratories, is a novel, highly-selective VMAT2 inhibitor that modulates dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines, thereby reducing the likelihood of "off-target" side effects. Valbenazine is designed to provide low, sustained, plasma and brain concentrations of active drug to minimize side effects associated with excessive monoamine depletion.
Modulation of neuronal dopamine levels in diseases such as tardive dyskinesia, Tourette syndrome, Huntington's chorea, schizophrenia, and tardive dystonia, which are characterized, in part, by a hyperdopaminergic state, should provide symptomatic benefits for patients with these diseases.
Neurocrine has received Breakthrough Therapy Designation from the FDA for valbenazine in the treatment of tardive dyskinesia and expects to file a New Drug Application for tardive dyskinesia in 2016.
Neurocrine Biosciences, Inc. discovers and develops innovative and life-changing pharmaceuticals, in diseases with high unmet medical needs, through its novel R&D platform, focused on neurological and endocrine based diseases and disorders.